A genomic clone containing a novel closely linked human histone H2A/H2B gene pair has been isolated and sequenced along with extensive 5' and 3' flanking regions. Both genes are devoid of introns and code for core histone proteins. The nucleotide sequences are 84% and 87% homologous to the coding regions of a human genomic H2A and H2B gene, respectively. A comparison of the nucleotide-derived amino acid sequences shows that the histone H2A protein corresponds to the human H2A.1 subtype, whereas the H2B histone gene predicts an H2B protein sequence which is almost identical to the histone H2B.2 variant from human and bovine obtained by direct protein sequencing. The 3' flanking regions contain previously identified conserved sequence elements thought to be involved in transcription termination and processing of replication-dependent histone gene poly(A)- mRNAs. Primer extension analyses of the histone mRNAs encoded within this clone demonstrate that both genes are divergently transcribed from a 313 bp intergene promoter region. The spatial arrangement and orientation of two TATA-boxes, four CAAT-boxes, and one H2B-box within this region suggests that the linked genes share common promoter elements for transcriptional regulation.